Chapter 3 - Impact of adolescent THC exposure on later adulthood: Focus on mesocorticolimbic function and behaviors

Abstract

There has been a recent increase in the use of Cannabis-based products containing high levels of Δ9-tetrahydrocannabinol (THC) by adolescents. We now know this impacts adolescent cognitive function during this critical period of brain development that results in affecting select brain functions in adulthood. In this chapter, we discuss the relationship between adolescent exposure to cannabinoids, brain development, and adulthood behavioral outcomes, with a focus on mesocorticolimbic function and behaviors. After reviewing how endocannabinoids (eCB) signaling is involved in brain development, we summarize evidence gathered in human adolescents focusing on how THC exposure changes brain anatomy, connectivity, and dopaminergic function in human adults. This evidence is placed in the context of the cognitive aptitude and behaviors of adolescents and their access to high THC products and novel delivery devices. We then summarize evidence in pre-clinical rodent models, including evidence gathered at the molecular and cellular levels showing how THC/cannabinoid exposure impacts the mesocorticolimbic system and reward/addiction-like behaviors in adulthood. These results are discussed in the context of our current understanding of cannabinoid pharmacokinetics (PK) and pharmacodynamics (PD), and the role of eCB signaling in adolescent brain development. Finally, we review novel experimental approaches to study adolescence self-administration of THC in rodents and results suggesting that cannabidiol (CBD) might alleviate the impact of THC on adolescent brains. Together, this chapter emphasizes the urgent need to address the increased use of high THC products by adolescents and study the mechanism by which THC impacts adolescent brain development to help discover viable therapeutic approaches.